Age- and brain region-specific differences in mitochondrial bioenergetics in Brown Norway rats

Jignesh D. Pandya; Joyce E. Royland; Robert C. MacPhail; Patrick G. Sullivan; Prasada Rao S. Kodavanti

doi:10.1016/j.neurobiolaging.2016.02.027

Age- and brain region-specific differences in mitochondrial bioenergetics in Brown Norway rats

Jignesh D. Pandya, Joyce E. Royland, Robert C. MacPhail, Patrick G. Sullivan, Prasada Rao S. Kodavanti

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bioenergetic parameters in 5 brain regions (brain stem [BS], frontal cortex, cerebellum, striatum, hippocampus [HIP]) of 4 diverse age groups (1 month [young], 4 months [adult], 12 months [middle-aged], 24 months [old age]) to understand age-related differences in selected brain regions and their possible contribution to age-related chemical sensitivity. Mitochondrial bioenergetic parameters and enzyme activities were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5/group). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State III respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V₁ and V₂) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12, and 24-months age groups. Activities of mitochondrial pyruvate dehydrogenase complex and electron transport chain complexes I, II, and IV enzymes were also age and brain region specific. In general, changes associated with age were more pronounced with enzyme activities declining as the animals aged (young > adult > middle-aged > old age). These age- and brain region-specific observations may aid in evaluating brain bioenergetic impact on the age-related susceptibility to environmental chemical stressors.

Original language	English
Pages (from-to)	25-34
Number of pages	10
Journal	Neurobiology of Aging
Volume	42
DOIs	https://doi.org/10.1016/j.neurobiolaging.2016.02.027
State	Published - Jun 1 2016

Bibliographical note

Funding Information:
This work was supported by US-EPA Contract RFQ-RT-12-140 (Jignesh D. Pandya and Patrick G. Sullivan, Co-PIs), NIH grants NS062993 (Patrick G. Sullivan) and NS069633 (Patrick G. Sullivan). The authors would like to thank Andrea Sebastian for expert technical assistance. Dr. Chris Gordon from NHEERL of USEPA, Dr. Steve Simmons from NCCT of USEPA, Research Triangle Park, NC, and Dr. Timothy Koves of Duke University, Durham, NC are acknowledged for their helpful comments on an earlier version of this manuscript. The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

Publisher Copyright:
© 2016.Published by Elsevier Inc.

Keywords

Aging
Bioenergetics
Brain regions
Enzyme activity
Mitochondria
Rats
Susceptibility

ASJC Scopus subject areas

Neuroscience (all)
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2016.02.027

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title = "Age- and brain region-specific differences in mitochondrial bioenergetics in Brown Norway rats",

abstract = "Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bioenergetic parameters in 5 brain regions (brain stem [BS], frontal cortex, cerebellum, striatum, hippocampus [HIP]) of 4 diverse age groups (1 month [young], 4 months [adult], 12 months [middle-aged], 24 months [old age]) to understand age-related differences in selected brain regions and their possible contribution to age-related chemical sensitivity. Mitochondrial bioenergetic parameters and enzyme activities were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5/group). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State III respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12, and 24-months age groups. Activities of mitochondrial pyruvate dehydrogenase complex and electron transport chain complexes I, II, and IV enzymes were also age and brain region specific. In general, changes associated with age were more pronounced with enzyme activities declining as the animals aged (young > adult > middle-aged > old age). These age- and brain region-specific observations may aid in evaluating brain bioenergetic impact on the age-related susceptibility to environmental chemical stressors.",

keywords = "Aging, Bioenergetics, Brain regions, Enzyme activity, Mitochondria, Rats, Susceptibility",

author = "Pandya, {Jignesh D.} and Royland, {Joyce E.} and MacPhail, {Robert C.} and Sullivan, {Patrick G.} and Kodavanti, {Prasada Rao S.}",

note = "Funding Information: This work was supported by US-EPA Contract RFQ-RT-12-140 (Jignesh D. Pandya and Patrick G. Sullivan, Co-PIs), NIH grants NS062993 (Patrick G. Sullivan) and NS069633 (Patrick G. Sullivan). The authors would like to thank Andrea Sebastian for expert technical assistance. Dr. Chris Gordon from NHEERL of USEPA, Dr. Steve Simmons from NCCT of USEPA, Research Triangle Park, NC, and Dr. Timothy Koves of Duke University, Durham, NC are acknowledged for their helpful comments on an earlier version of this manuscript. The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use. Publisher Copyright: {\textcopyright} 2016.Published by Elsevier Inc.",

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AU - Royland, Joyce E.

AU - MacPhail, Robert C.

AU - Sullivan, Patrick G.

AU - Kodavanti, Prasada Rao S.

N1 - Funding Information: This work was supported by US-EPA Contract RFQ-RT-12-140 (Jignesh D. Pandya and Patrick G. Sullivan, Co-PIs), NIH grants NS062993 (Patrick G. Sullivan) and NS069633 (Patrick G. Sullivan). The authors would like to thank Andrea Sebastian for expert technical assistance. Dr. Chris Gordon from NHEERL of USEPA, Dr. Steve Simmons from NCCT of USEPA, Research Triangle Park, NC, and Dr. Timothy Koves of Duke University, Durham, NC are acknowledged for their helpful comments on an earlier version of this manuscript. The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use. Publisher Copyright: © 2016.Published by Elsevier Inc.

PY - 2016/6/1

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N2 - Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bioenergetic parameters in 5 brain regions (brain stem [BS], frontal cortex, cerebellum, striatum, hippocampus [HIP]) of 4 diverse age groups (1 month [young], 4 months [adult], 12 months [middle-aged], 24 months [old age]) to understand age-related differences in selected brain regions and their possible contribution to age-related chemical sensitivity. Mitochondrial bioenergetic parameters and enzyme activities were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5/group). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State III respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12, and 24-months age groups. Activities of mitochondrial pyruvate dehydrogenase complex and electron transport chain complexes I, II, and IV enzymes were also age and brain region specific. In general, changes associated with age were more pronounced with enzyme activities declining as the animals aged (young > adult > middle-aged > old age). These age- and brain region-specific observations may aid in evaluating brain bioenergetic impact on the age-related susceptibility to environmental chemical stressors.

AB - Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bioenergetic parameters in 5 brain regions (brain stem [BS], frontal cortex, cerebellum, striatum, hippocampus [HIP]) of 4 diverse age groups (1 month [young], 4 months [adult], 12 months [middle-aged], 24 months [old age]) to understand age-related differences in selected brain regions and their possible contribution to age-related chemical sensitivity. Mitochondrial bioenergetic parameters and enzyme activities were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5/group). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State III respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12, and 24-months age groups. Activities of mitochondrial pyruvate dehydrogenase complex and electron transport chain complexes I, II, and IV enzymes were also age and brain region specific. In general, changes associated with age were more pronounced with enzyme activities declining as the animals aged (young > adult > middle-aged > old age). These age- and brain region-specific observations may aid in evaluating brain bioenergetic impact on the age-related susceptibility to environmental chemical stressors.

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KW - Susceptibility

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ER -

Age- and brain region-specific differences in mitochondrial bioenergetics in Brown Norway rats

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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